From hidden immunodeficiency to hyperinflammatory crisis: Cryptococcosis-induced HLH in adult-onset severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is classically a pediatric disease, yet rare late-onset forms can present in adulthood with atypical infections. We report a 42-year-old man presenting with febrile illness, hepatosplenomegaly, and pancytopenia. Bone marrow examination revealed intracellular fungal organisms, morphologically suggestive of Cryptococcus infection. The absence of known immunosuppressive states prompted immunophenotyping, which demonstrated profound B, T, and NK cell lymphopenia, consistent with SCID or late-onset combined immunodeficiency. The patient was initiated on systemic antifungal therapy; however, his condition deteriorated rapidly and he succumbed to death within three days. To ascertain the exact cause of death, a postmortem bone marrow biopsy was performed, which revealed progression to hemophagocytic lymphohistiocytosis, explaining the fulminant clinical decline. This case highlights the importance of considering underlying primary immunodeficiency in adults presenting with opportunistic fungal infections, as these conditions can rapidly progress to fulminant, life-threatening complications with high mortality.